Abstract
The rates of conversion into 14CO2 of D-(-)-3-hydroxy[3-14C]butyrate, [3-14C]acetoacetate, [6-14C]glucose and [U-14C]glutamine were measured in the presence and absence of unlabelled alternative oxidizable substrates in whole homogenates from the brains of young and adult rats. The addition of unlabelled glutamine resulted in decreased 14CO2 production from [6-14C]glucose in brain homogenates from both young and adult rats. In contrast, glucose had no effect on [U-14C]glutamine oxidation. In suckling animals, both 3-hydroxybutyrate and acetoacetate decreased the rate of oxidation of [6-14C]glucose, but in adults only 3-hydroxybutyrate had an effect, and to a lesser degree. The addition of unlabelled glucose markedly enhanced the rates of oxidation of both ketone bodies in adult brain tissue and had little or no effect in the young. The rate of production of 14CO2 from [U-14C]glutamine was increased by the addition of unlabelled ketone bodies in brain homogenates from young, but not from adult rats. In the converse situation, unlabelled glutamine added to 14C-labelled ketone bodies diminished 14CO2 production in young rats, but had no effect in adult animals. These results revealed a complex age-dependent pattern of interaction in which certain substrates apparently competed with each other, whereas an enhanced rate of 14CO2 production was found with others.
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- Benjamin A. M., Quastel J. H. Fate of L-glutamate in the brain. J Neurochem. 1974 Sep;23(3):457–464. doi: 10.1111/j.1471-4159.1974.tb06046.x. [DOI] [PubMed] [Google Scholar]
- Bradford H. F., Ward H. K., Thomas A. J. Glutamine--a major substrate for nerve endings. J Neurochem. 1978 Jun;30(6):1453–1459. doi: 10.1111/j.1471-4159.1978.tb10477.x. [DOI] [PubMed] [Google Scholar]
- Cremer J. E. Nutrients for the brain: problems in supply. Early Hum Dev. 1981 May;5(2):117–132. doi: 10.1016/0378-3782(81)90043-8. [DOI] [PubMed] [Google Scholar]
- Dienel G., Ryder E., Greengard O. Distribution of mitochondrial enzymes between the perikaryal and synaptic fractions of immature and adult rat brain. Biochim Biophys Acta. 1977 Feb 28;496(2):484–494. doi: 10.1016/0304-4165(77)90330-0. [DOI] [PubMed] [Google Scholar]
- Gjedde A., Crone C. Induction processes in blood-brain transfer of ketone bodies during starvation. Am J Physiol. 1975 Nov;229(5):1165–1169. doi: 10.1152/ajplegacy.1975.229.5.1165. [DOI] [PubMed] [Google Scholar]
- Hawkins R. A., Biebuyck J. F. Ketone bodies are selectively used by individual brain regions. Science. 1979 Jul 20;205(4403):325–327. doi: 10.1126/science.451608. [DOI] [PubMed] [Google Scholar]
- Häussinger D., Gerok W., Sies H. Inhibition of pyruvate dehydrogenase during the metabolism of glutamine and proline in hemoglobin-free perfused rat liver. Eur J Biochem. 1982 Aug;126(1):69–76. doi: 10.1111/j.1432-1033.1982.tb06747.x. [DOI] [PubMed] [Google Scholar]
- Ito T., Quastel J. H. Acetoacetate metabolism in infant and adult rat brain in vitro. Biochem J. 1970 Feb;116(4):641–655. doi: 10.1042/bj1160641. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jope R. S. Acetylcholine turnover and compartmentation in rat brain synaptosomes. J Neurochem. 1981 May;36(5):1712–1721. doi: 10.1111/j.1471-4159.1981.tb00423.x. [DOI] [PubMed] [Google Scholar]
- Keller K., Lange K., Noske W. D-Glucose transport in cultured cells of neural origin: the membrane as possible control point of glucose utilization. J Neurochem. 1981 Mar;36(3):1012–1017. doi: 10.1111/j.1471-4159.1981.tb01694.x. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Lai J. C., Walsh J. M., Dennis S. C., Clark J. B. Synaptic and non-synaptic mitochondria from rat brain: isolation and characterization. J Neurochem. 1977 Mar;28(3):625–631. doi: 10.1111/j.1471-4159.1977.tb10434.x. [DOI] [PubMed] [Google Scholar]
- Nicklas W. J., Browning E. T. Amino acid metabolism in glial cells: homeostatic regulation of intra- and extracellular milieu by C-6 glioma cells. J Neurochem. 1978 May;30(5):955–963. doi: 10.1111/j.1471-4159.1978.tb12387.x. [DOI] [PubMed] [Google Scholar]
- Nicklas W. J., Browning E. T. Glutamate uptake and metabolism in C-6 glioma cells: alterations by potassium ion and dibutyryl cAMP. J Neurochem. 1983 Jul;41(1):179–187. doi: 10.1111/j.1471-4159.1983.tb13667.x. [DOI] [PubMed] [Google Scholar]
- Nicklàs W. J., Nunez R., Berl S., Duvoisin R. Neuronal-glial contributions to transmitter amino acid metabolism: studies with kainic acid-induced lesions of rat striatum. J Neurochem. 1979 Oct;33(4):839–844. doi: 10.1111/j.1471-4159.1979.tb09913.x. [DOI] [PubMed] [Google Scholar]
- Page M. A., Krebs H. A., Williamson D. H. Activities of enzymes of ketone-body utilization in brain and other tissues of suckling rats. Biochem J. 1971 Jan;121(1):49–53. doi: 10.1042/bj1210049. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Patel M. S., Owen O. E. Development and regulation of lipid synthesis from ketone bodies by rat brain. J Neurochem. 1977 Jan;28(1):109–114. doi: 10.1111/j.1471-4159.1977.tb07715.x. [DOI] [PubMed] [Google Scholar]
- Pleasure D., Lichtman C., Eastman S., Lieb M., Abramsky O., Silberberg D. Acetoacetate and D-(-)-beta-hydroxybutyrate as precursors for sterol synthesis by calf oligodendrocytes in suspension culture: extramitochondrial pathway for acetoacetate metabolism. J Neurochem. 1979 May;32(5):1447–1450. doi: 10.1111/j.1471-4159.1979.tb11083.x. [DOI] [PubMed] [Google Scholar]
- Pollay M., Stevens F. A. Starvation-induced changes in transport of ketone bodies across the blood-brain barrier. J Neurosci Res. 1980;5(2):163–172. doi: 10.1002/jnr.490050208. [DOI] [PubMed] [Google Scholar]
- Reed W. D., Zielke H. R., Baab P. J., Ozand P. T. Ketone bodies, glucose and glutamine as lipogenic precursors in human diploid fibroblasts. Lipids. 1981 Sep;16(9):677–684. doi: 10.1007/BF02535063. [DOI] [PubMed] [Google Scholar]
- Robinson A. M., Williamson D. H. Physiological roles of ketone bodies as substrates and signals in mammalian tissues. Physiol Rev. 1980 Jan;60(1):143–187. doi: 10.1152/physrev.1980.60.1.143. [DOI] [PubMed] [Google Scholar]
- Roeder L. M., Poduslo S. E., Tildon J. T. Utilization of ketone bodies and glucose by established neural cell lines. J Neurosci Res. 1982;8(4):671–682. doi: 10.1002/jnr.490080412. [DOI] [PubMed] [Google Scholar]
- Roeder L. M., Tildon J. T., Holman D. C. Competition among oxidizable substrates in brains of young and adult rats. Dissociated cells. Biochem J. 1984 Apr 1;219(1):131–135. doi: 10.1042/bj2190131. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roeder L. M., Tildon J. T., Reed W. D., Ozand P. T. The effects of ketone bodies, bicarbonate, and calcium on hepatic mitochondrial ketogenesis. Arch Biochem Biophys. 1982 Sep;217(2):460–467. doi: 10.1016/0003-9861(82)90524-0. [DOI] [PubMed] [Google Scholar]
- Smith C. M., Bryla J., Williamson J. R. Regulation of mitochondrial alpha-ketoglutarate metabolism by product inhibition at alpha-ketoglutarate dehydrogenase. J Biol Chem. 1974 Mar 10;249(5):1497–1505. [PubMed] [Google Scholar]
- Tildon J. T., Cone A. L., Cornblath M. Coenzyme A transferase activity in rat brain. Biochem Biophys Res Commun. 1971 Apr 2;43(1):225–231. doi: 10.1016/s0006-291x(71)80111-0. [DOI] [PubMed] [Google Scholar]
- Tildon J. T., Merrill S., Roeder L. M. Differential substrate oxidation by dissociated brain cells and homogenates during development. Biochem J. 1983 Oct 15;216(1):21–25. doi: 10.1042/bj2160021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tildon J. T., Roeder L. M. Glycerol oxidation in rat brain: subcellular localization and kinetic characteristics. J Neurosci Res. 1980;5(1):7–17. doi: 10.1002/jnr.490050103. [DOI] [PubMed] [Google Scholar]
- Weber G. Inhibition of human brain pyruvate kinase and hexokinase by phenylalanine and phenylpyruvate: possible relevance to phenylketonuric brain damage. Proc Natl Acad Sci U S A. 1969 Aug;63(4):1365–1369. doi: 10.1073/pnas.63.4.1365. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weber G., Lea M. A., Stamm N. B. Sequential feedback inhibition and regulation of liver carbohydrate metabolism through control of enzyme activity. Adv Enzyme Regul. 1968;6:101–123. doi: 10.1016/0065-2571(68)90009-5. [DOI] [PubMed] [Google Scholar]